Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.     

Quantitative risk assessment using a Japanese hydrogen refueling station model

Although hydrogen refueling stations (HRSs) are becoming widespread across Japan and are essential for the operation of fuel cell vehicles, they present potential hazards. A large number of accidents such as explosions or fires have been reported, rendering it necessary to conduct a number of qualitative and quantitative risk assessments for HRSs. Current safety codes and technical standards related to Japanese HRSs have been established based on the results of a qualitative risk assessment and quantitative effectiveness validation of safety measures over ten years ago. In the last decade, there has been much development in the technologies of the components or facilities used in domestic HRSs and much operational experience as well as knowledge to use hydrogen in HRSs safely have been gained through years of commercial operation. The purpose of the present study is to conduct a quantitative risk assessment (QRA) of the latest HRS model representing Japanese HRSs with the most current information and to identify the most significant scenarios that pose the greatest risks to the physical surroundings in the HRS model. The results of the QRA show that the risk contours of 10^?3 and 10^?4 per year were confined within the HRS boundaries, whereas the risk contours of 10^?5 and 10^?6 per year are still present outside the HRS. Comparing the breakdown of the individual risks (IRs) at the risk ranking points, we conclude that the risk of jet fire demonstrates the highest contribution to the risks at all of the risk ranking points and outside the station. To reduce these risks and confine the risk contour of 10^?6 per year within the HRS boundaries, it is necessary to consider risk mitigation measures for jet fires.     

Direct Observation of Pure Cu and Cu-Ag Anode Passivation in H2SO4-CuSO4 Aqueous Solution by Channel Flow Double Electrode and Optical Microscopy

Metallurgical and Materials Transactions B - The dissolution and passivation of pure Cu and Cu-5 wt pct Ag anodes in H2SO4-CuSO4 electrolyte were investigated by a direct...     

The method of double averaging: an approach for modeling power-factor-correction switching converters

This paper describes the modeling of power-factor-correction converters under average-current-mode control, which are widely used in switch-mode power supply applications. The objective is to identify stability boundaries in terms of major circuit parameters for facilitating design of such converters. The approach employs a double averaging procedure, which first applies the usual averaging over the switching period and subsequently applies generalized averaging over the mains period. The resulting model, after two averaging steps and application of a harmonic balance procedure, is nonlinear and capable of describing the low-frequency nonlinear dynamics of the system. The parameter ranges within which stable operation is guaranteed can be accurately and easily found using this model. Experimental measurements are provided for verification of the analytical results.     

Synthesis and photosensitivity of acryloylmorpholine copolymers with a pendant (meth)acryloyl group

We have developed new photopolymers that have superior waterproof properties and that can easily interact with polyfunctional acrylate compounds, thus serving as hydrophobic photocrosslinking reagents. Acryloylmorpholine monomers whose homopolymers were less moisture absorbing than the usual water‐soluble polymers but were still water soluble to a good degree, were copolymerized with other acryloyl monomers. We then introduced the photosensitive (meth)acryloyl group to side chains of the resulting polymers. Among six copolymers examined, the copolymers composed of acryloyl morpholine, hydroxyethyl acrylate, ethyl, or methyl methacrylate, and methacryloyl isocyanate were found to have nicely balanced hydrophilicity and waterproof properties, in addition to good compatibility with hydrophobic photocrosslinking reagents. The composite polymers thus obtained were confirmed to be promising photopolymers usable even in a highly humid environment. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 684–692, 2003     

Stability,cure properties,and applicability as one part adhesives of systems of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisepoxide

Heterogeneous curable compositions of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisphenol A diglycidyl ether (BADG) systems were prepared by merely mixing these components at room temperature. Stability at room temperature and cure properties at high temperature of the compositions were investigated for evaluating their applicability as one part adhesive. It was found that the systems containing Mg were generally more stable than those containing Ca. Similarly, at 150°C the Ca-containing systems showed generally shorter gelation time than the Mg-containing ones, due to the fact that the Ca salt dissolves more rapidly and enters into the addition reaction with the anhydride, leading to the faster appearance of the catalytic activities of the Ca carboxylate group. Among the various combinations of components, the metal salt–succinic anhydride (SA)–BADG systems were stable at room temperature for more than 6 months and rapidly cured at high temperature, showing excellent adhesive properties. This result indicates that the SA-containing systems should be of interest in applications to one part adhesives.     

Galvanic cell measurements on supersaturated activities of oxygen in Fe-Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) melts

Using a mullite (3Al₂O₃ · 2SiO₂)-tube and ZrO₂-9 mol pct MgO-plug type solid electrolyte galvanic cells, the activities of supersaturated oxygen in Fe-0.0017 to 0.41 mass pct Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) alloys were measured as a function of total Al or M contents at 1873 K in an alumina crucible. Based on these results, the effects of alloying elements on the supersaturated oxygen activity with respect to alumina precipitation were studied. In the Fe-Al-M (M=C, Te, Mn, Cr, and Si) alloys, the supersaturated oxygen activities for a given Al level approach the equilibrium values with increasing contents of alloying elements. However, the oxygen activities for a given Al level are still supersaturated in the Fe-Al-M (M=Ti, Zr, and Ce) alloys even in the presence of considerable amounts of the alloying elements.